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Carnosic acid sensitized TRAIL-mediated apoptosis through down-regulation of c-FLIP and Bcl-2 expression at the post translational levels and CHOP-dependent up-regulation of DR5, Bim, and PUMA expression in human carcinoma caki cells

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Author(s)
Kyong-Jin JungKyoung-jin MinJae Hoon BaeTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg KyuBae, Jae Hoon
Department
Dept. of Immunology (면역학)
Dept. of Physiology (생리학)
Journal Title
Oncotarget
Issued Date
2015
Volume
6
Issue
3
Keyword
Carnosic acidTRAILBcl-2c-FLIPCHOP
Abstract
Carnosic acid is a phenolic diterpene from rosmarinus officinalis, and has multiple
functions, such as anti-inflammatory, anti-viral, and anti-tumor activity. In this study,
we examined whether carnosic acid could sensitize TRAIL-mediated apoptosis in
human renal carcinoma Caki cells. We found that carnosic acid markedly induced
TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), and
human hepatocellular carcinoma (SK-HEP-1), and human breast carcinoma (MDAMB-
231) cells, but not normal cells (TMCK-1 and HSF). Carnosic acid induced downregulation
of c-FLIP and Bcl-2 expression at the post-translational levels, and the
over-expression of c-FLIP and Bcl-2 markedly blocked carnosic acid-induced TRAIL
sensitization. Furthermore, carnosic acid induced death receptor (DR)5, Bcl-2
interacting mediator of cell death (Bim), and p53 up-regulated modulator of apoptosis
(PUMA) expression at the transcriptional levels via CCAAT/enhancer-binding proteinhomologous
protein (CHOP). Down-regulation of CHOP expression by siRNA inhibited
DR5, Bim, and PUMA expression, and attenuated carnosic acid plus TRAIL-induced
apoptosis. Taken together, our study demonstrates that carnosic acid enhances
sensitization against TRAIL-mediated apoptosis through the down-regulation of
c-FLIP and Bcl-2 expression, and up-regulation of ER stress-mediated DR5, Bim, and
PUMA expression at the transcriptional levels.
Keimyung Author(s)(Kor)
권택규
배재훈
Publisher
School of Medicine
Citation
Kyong-Jin Jung et al. (2015). Carnosic acid sensitized TRAIL-mediated apoptosis through down-regulation of c-FLIP and Bcl-2 expression at the post translational levels and CHOP-dependent up-regulation of DR5, Bim, and PUMA expression in human carcinoma caki cells. Oncotarget, 6(3), 1556–1568. doi: 10.18632/oncotarget.2727
Type
Article
ISSN
1949-2553
DOI
10.18632/oncotarget.2727
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33613
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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